Coronary Microvascular Dysfunction May Be a Marker of CV Risk in Obese Patients

The presence of coronary microvascular dysfunction may be a better predictor of adverse events in patients with suspected CAD than body mass index (BMI) or traditional risk factors alone, a new study suggests. Assessment of the microvasculature may be particularly important in clarifying risk in obese patients and assessing them for weight-loss interventions and pharmacologic therapies.

All patients in the study, both obese and nonobese, underwent positron emission tomography (PET) scanning, with noninvasive calculation of coronary flow reserve (CFR). Having a BMI of ≥ 30 was independently associated with lower CFR. At a CFR of ≤ 1.7, obese individuals had a more than twofold increased risk of cardiac events.

Deepak Bhatt, MD (Brigham and Women’s Hospital, Boston, MA), one of the study’s co-authors, said that while the paper is not advocating PET scanning for everyone with suspected CAD, it demonstrates the technology is making inroads in the understanding of coronary microvascular dysfunction.

“It’s very useful information when you’re trying to figure out whether someone referred for cardiac stress testing for chest pain is having pain due to epicardial disease or microvascular dysfunction, or some combination of the two,” he said in an interview with TCTMD. Additionally, Bhatt said, it can provide clearer assessment in obese patients who may otherwise have inaccurate results on a standard cardiac single-photon emission computerized tomography (SPECT) scan or treadmill test.

The study was published online August 6, 2018, ahead of print in the Journal of the American College of Cardiology.

Event Rate Increases as Flow Reserve Decreases

Led by Navkaranbir S. Bajaj, MD (Brigham and Women’s Hospital, Boston, MA), the study looked at 827 patients with normal perfusion who were followed over 5.6 years. Of these, 398 were obese, with 233 individuals meeting recommendations for bariatric surgery eligibility. Obese patients were more likely than those who were not obese to be younger, female, and nonwhite. They also had higher rates of hypertension, diabetes, antihypertensive and insulin use, higher estimated glomerular filtration rate, and lower CFR.

There was no significant interaction between BMI and CFR on outcomes. Compared with traditional risk factors including BMI, CFR was the largest prognostic contributor to risk of adverse events, defined as a composite of death or hospitalization for nonfatal MI or heart failure. At a CFR value of < 1.7, there was a “steep increase in the annualized event risk to approximately 3%,” Bajaj et al report. Furthermore, when the obese cohort was stratified by CFR, a level of < 1.7 was associated with a significant increase in adjusted cumulative hazard (HR 2.28; 95% CI 1.36-3.81). Impaired CFR in obese patients also predicted a higher adjusted annualized rate of adverse events compared with nonobese patients (5.7% vs 2.6%; P = 0.002).

“Along with surgical weight loss, novel therapies targeting residual cholesterol or inflammatory risk, and neurohormonal activation or glucose handling in the kidneys, may improve coronary microvascular dysfunction in this sector of patients and shift individuals from a high- to low-risk obesity phenotype,” the researchers write. They add that this may be particularly important to address in women, who seem to be overrepresented when it comes to microvascular dysfunction.

Resurgence of Interest in the Microvasculature

“There clearly is a contingent of patients who have coronary microvascular dysfunction. They clearly have symptoms, and maybe we should investigate some novel therapies in these folks to make them feel better and maybe even help them live longer,” Bhatt said.

Although the microvasculature is not routinely the subject of investigation in most patients seen in cath labs, he noted that there was a time when it was being actively researched.

“It may be time for a renaissance of this type of research,” he observed. “About 20 years ago FFR and CFR were being assessed fairly frequently, but it fell out of favor because it wasn't clear that it was useful. CFR from an interventionalist perspective is not that hard to do and may be something that can be done at the same time as angiography in some patients.”

In a person with microvascular disease, maybe the stenting in and of itself is not going to be sufficient. Deepak Bhatt

In the aftermath of ORBITA, Bhatt said, addressing why some patients do not get substantial relief of angina from stenting is an important topic, and one that may merge with microvasculature research. Using modalities such as PET scanning with other traditional testing, he added, could provide a “holistic assessment” of a patient’s chest pain and also help researchers understand ways to predict whether stenting a certain lesion will alleviate pain.

“In a person with microvascular disease, maybe the stenting in and of itself is not going to be sufficient,” Bhatt said. “Right now, many physicians aren’t going to know what to do when presented with information on microvascular disease, so we need to gather more data in the contemporary setting and we also need to see whether invasively-defined CFR affects management in a way that improves either hard outcomes, or relief of angina.”

Importance of Obesity Connection

In an editorial accompanying the study, Thomas H. Schindler, MD (Washington University School of Medicine, St. Louis, MO), writes that the study provides “important evidence that obesity in cardiovascular risk individuals is not just an epiphenomenon, but rather it actively contributes to the manifestation of coronary microvascular dysfunction associated with adverse cardiac outcome.”

In addition to controlling cardiac risk factors, Schindler suggests that treatment strategies “should always imply weight reduction and continuous physical exercise in obese individuals, independent of the presence or absence of coronary microvascular dysfunction.”

In an email, Carl Lavie, MD (Ochsner Heart and Vascular Institute, New Orleans, LA), told TCTMD it is well-recognized that obesity increases the risk of heart failure, especially in the presence of other risk factors such as endothelial dysfunction, diabetes, and hypertension. He noted that the study did not assess fitness, which is a major predictor of prognosis and heart failure, as well as of CVD- and all-cause mortality.

“It is well known that one of the best ways to improve endothelial function is with exercise training, as well as weight reduction,” Lavie added. “Still, this study makes some important points linking obesity and microvascular coronary dysfunction and reduced coronary flow reserve, the latter with increased risk of poor outcomes.”